Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1971. / Includes bibliographical references. / by William W. Walker, Jr. / M.S.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1991. / Includes bibliographical references. / by Moira Marx Nir. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, February 2011. / "October 2010." Cataloged from PDF version of thesis. / Includes bibliographical references (p. 140-147). / Rapid genome characterization is one of the grand challenges of genome science today. Although the complete sequences of certain representative human genomes have been determined, genomes from a much larger number of individuals are yet to be studied in order to fully understand genome diversity and genetic diseases. While current state-of-the-art sequencing technologies are limited by the large timescale and cost required to analyze a single sample, an alternative strategy termed DNA mapping has recently received considerable attention. Unlike sequencing which produces single-base resolution, DNA mapping resolves coarse-scale (~kbp) information of the sequence, which is much faster and cheaper to obtain, but still sufficient to discern genomic differences among individuals within a given species. Advances in fluorescence microscopy have allowed the possibility to directly map a single DNA molecule. This concept, though straightforward, faces a major challenge that the entropic tendency of polymeric DNA to adopt a coiled conformation must be overcome so as to optically determine the position of specific sequences of interest on the DNA backbone. The ability to control and manipulate the conformation of single DNA molecules, especially, to stretch them into a linear format in a consistent and uniform manner, is thus crucial to the performance of such mapping devices. The focus of this thesis is to develop a reliable single DNA stretching device that can be used in single molecule DNA mapping, and to experimentally probe the fundamental physics that govern DNA deformation. In the aspect of device design, the strategy we pursue is the use of an elongational electric field with a stagnation point generated in the center of a cross-slot or T channel to stretch DNA molecules. The good compatibility of electric field with small channel dimensions allows us to use micro- or nano-fabricated channels with height on the order of or smaller than the natural size of DNA to keep the molecule always in focus, a feature desirable for any mapping applications. The presence of the stagnation point allows the possibility to dynamically trap and stretch single DNA molecules. This trapping capability ensures uniform stretching within a sample ensemble, and also allows prolonged imaging time to obtain accurate detection results. We primarily investigate the effects of channel height on the stretching process, specifically, we seek the possibility of utilizing slit-like nanoconfinement to aid DNA stretching. Although extensive previous studies have demonstrated that geometric confinement of DNA can substantially alter the conformation and dynamics of these molecules at equilibrium, no direct studies of this non-equilibrium stretching process in confinement exist prior to the work presented in this thesis. We find that slit-like confinement indeed facilitates DNA stretching by reducing the deformation Abstract rate required to achieve a certain extension. However, due to the fact that the steric interactions between the DNA and the confining walls vanish at large extensions, highly stretched DNA under confinement behaves qualitatively similar to unconfined DNA except with screened hydrodynamic interactions, and a new time scale arises that should be used to describe the large change in extension with applied deformation rate. In a consecutive study, we examine the low-extension stretching process and observe a strongly modified coil-stretch transition characterized by two distinct critical deformation rates for DNA in confinement, different from the unconfined case where a single critical deformation rate exists. With kinetic theory modeling, we demonstrate that the two-stage coilstretch transition in confinement is induced by a modified spring force law, which is essentially related to the extension-dependent steric interactions between DNA and the confining walls. We also study aspects of the equilibrium conformation and dynamics of DNA in slit-like confinement in order to provide insight into regimes where existing studies show inconsistent results. We use both experiments and simulations to demonstrate that the in-plane radius of gyration and the 3D radius of gyration of DNA behaves differently in weak confinement. In strong confinement, we do not identify any evident change in the scalings of equilibrium size, diffusivity, and longest relaxation time of the DNA with channel height from the de Gennes regime to the Odijk regime. Although the transition between the de Gennes and Odijk regimes in slit-like confinement still remains an open question, our finding adds more experimental evidence to the side of a continuous transition. The impact of this thesis will be two-fold. We design a DNA stretching device that is readily applicable to single molecule DNA mapping and establish guidelines for the effective operation of the device. Our fundamental results regarding both the equilibrium and non-equilibrium dynamics of DNA molecules in slit-like confinement will serve as a solid basis for both the design of future devices aiming to exploit confinement to manipulate biopolymers, and more complicated studies of confined polymer physics. / by Jing Tang. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1989. / Includes bibliographical references (leaves 242-273). / by Ludwig C. Nitsche. / Ph.D.

Thesis (M.S.) Massachusetts Institute of Technology. Dept. of Chemical Engineering, 1945. / Bibliography: leaf 56. / by Kia-Ting Wang. / M.S.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2008. / Includes bibliographical references (p. 166-176). / Electrospinning has emerged in recent years as a relatively easy, efficient and robust method to make ultrafine continuous fibers with diameter on the order of -100 nm from a variety of materials. As a result, numerous applications for electrospun fibers have already been demonstrated including the commercialized ones in the areas of filtration and tissue engineering. However, in most cases, the nanofibers are homogeneous; the development of external and internal nanostructures could significantly expand the applications of these fibers. The goal of this dissertation is therefore to develop controllable nanostructures for electrospun fibers with an emphasis on the understanding of structure formation and explore their unique applications. Specifically, this dissertation can be divided into two areas. The first part is related to superhydrophobic or "self-cleaning" surfaces. This has been a hot research area due to the wide applications of such materials. Electrospun fibers were first discovered in this dissertation to have sufficient surface roughness for superhydrophobic effect. In contrast to many conventional superhydrophobic surfaces, those composed of electrospun fibers are flexible, breathable and free-standing. It has been demonstrated that superhydrophobic fabrics can be made by either electrospinning a hydrophobic material or applying post-treatment to electrospun mats (e.g. through initiated chemical vapor deposition). Based on an understanding of the role of fibrous structure to create a surface of suitable topology, different strategies have been invented to enhance the superhydrophobic property and its robustness by carefully designing the external nanostructures of individual fibers using various methods such as layer-by-layer assembly. Other functionalities such as transparency and fluorescence were successfully incorporated into superhydrophobic surfaces. In particular, superhydrophobic fibrous membranes with structural colors as those displayed by some beautiful butterfly wings were produced. Besides making superhydrophobic materials from the externally nanostructured fibers, internally nanostructured electrospun fibers were also developed through the microphase separation of cylindrically confined block copolymer systems. / (cont.) This is the second part of this dissertation. Continuous nanofibers with long range order internal structure were obtained by two-fluid coaxial electrospinning in which the desired block copolymer is encapsulated as the core component within a polymer shell having a high glass transition temperature (Tg), followed by proper thermal annealing of the fibers. Various interesting, unusual and sometimes unprecedented self-assembly structures of block copolymers under cylindrical confinement have been observed. Based on quantitative analyses, the confinement was found to affect both phase type and fundamental domain sizes of the block copolymer. These internally nanostructured fibers have both practical and fundamental intellectual importance. For example, these nanofibers have unique potential for applications in optics, photonics, drug delivery, and other uses because of their small diameter, unique internal structure, and continuous filamentary nature. / by Minglin Ma. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2012. / Vita. Cataloged from PDF version of thesis. / Includes bibliographical references (p. 95-104). / Host response to implanted biomaterials and medical devices poses tremendous challenges to their clinical applications. Today, the quest to mitigate this immunological attack for improved longevity of these devices remains daunting. This thesis aims to explore the use of anti-inflammatory drugs in minimizing the host response and improve the efficacy of implantable and transplantable therapeutics. Firstly, we developed a new non-invasive in vivo imaging technique to study the activity of early immune cells in the host response to implanted biomaterials. A fluorescent imaging probe (Prosense680*, Perkin Elmer) activatable by cathepsins, a class of inflammatory proteases secreted from immune cells, was used for simultaneous biocompatibility screening of up to 8 different materials per animal in immunocompetent hairless SKH1E mice. In this assay, the different biocompatibility properties of polystyrene beads, alginate and saline were correlated with varying levels of cathepsin activities as acquired by imaging. Comparison of the imaging results with traditional histological analysis validated that this new fluorescent imaging technique can be used to assess material biocompatibility efficiently and rapidly. We applied this new fluorescent imaging technique to investigate the in vivo spatial and temporal host response to a subcutaneously-injected, controlled-release anti-inflammatory drug formulation. Poly-lactic-coglycolic (PLGA) microparticles with low loading (1.3wt%) of dexamethasone locally inhibited the activity of cathepsin enzymes from immune cells, while high drug loading formulation (26wt%) resulted in systemic immunosuppression. We also showed that incorporation of dexamethasone at a low loading (1.3wt%) attenuated the coverage of polymeric microparticles by immune cell layers. Temporal monitoring of the drug effect confirmed that incorporation of dexamethasone decreased early enzymatic activity and long-term cellular infiltration to implanted materials. Next, we performed in vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs (NSAIDs, polyphenols, glucocorticoids and other non-steroidal immunosuppressants) encapsulated in PLGA microparticles in immunocompetent hairless SKH-1E mice. Using non-invasive fluorescent imaging coupled with parallel bioluminescent imaging, we identified dexamethasone and curcumin as the most effective drugs in inhibiting the activities of inflammatory proteases and reactive oxygen species respectively. Histological analysis also showed that dexamethasone and curcumin encapsulated in PLGA microparticles decreased subsequent cellular infiltration and fibrosis formation surrounding the subcutaneously injected PLGA microparticles for up to 4 weeks and 2 weeks respectively. Lastly, we designed hybrid alginate hydrogel microcapsules co-encapsulating pancreatic rat islets and dexamethasone or curcumin. Uniform spherical microcapsules containing homogeneously distributed dexamethasone (2mg/ml) or curcumin (1mg/ml) were transplanted into streptozotocin-induced C57B6/J diabetic mice. Using a marginal islet mass of 250 islet equivalents, curcumin-loaded capsules effectively improved glycemic control by increasing the graft survival time to 30 days compared to 15 and 21 days by control and dexamethasone-containing capsules respectively. Curcumin also significantly reduced fibrotic overgrowth on the encapsulated islets explanted on day 60 as evidenced by DNA fluorescent staining of the fibrotic cell layers on the surface of the retrieved capsules. Taken together, the results of this thesis demonstrate that anti-inflammatory drugs have the potential to minimize the attack by host immune system and improve the efficacy or functional longevity of cell-based therapeutics and possibly other implantable medical devices. / by Thuy Tram Dang. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2013. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Cataloged from student-submitted PDF version of thesis. / Includes bibliographical references (p. 229-238). / This thesis addresses the problem of worst-case steady-state design of process systems under uncertainty, also known as robust design. Designing for the worst case is of great importance when considering systems for deployment in extreme and hostile environments, where operational failures cannot be risked due to extraordinarily high economic and/or environmental expense. For this unique scenario, the cost of "over-designing" the process far outweighs the cost associated with operational failure. Hence, it must be guaranteed that the process is sufficiently robust in order to avoid operational failures. Many engineering, economic, and operations research applications are concerned with worst-case scenarios. Classically, these problems give rise to a type of leader-follower game, or Stackelberg game, commonly known as the "minimax" problem, or more precisely as a max-min or min-max optimization problem. However, since the application here is to steady-state design, the problem formulation results in a more general nonconvex equality-constrained min-max program, for which no previously available algorithm can solve effectively. Under certain assumptions, the equality constraints, which correspond to the steady-state model, can be eliminated from the problem by solving them for the state variables as implicit functions of the control variables and uncertainty parameters. This approach eliminates explicit functional dependence on the state variables, and in turn reduces the dimensionality of the original problem. However, this embeds implicit functions in the program, which have no explicit algebraic form and can only be approximated using numerical methods. By doing this, the max-min program can be reformulated as a more computationally tractable semi-infinite program, with the caveat that there are embedded implicit functions. Semi-infinite programming with embedded implicit functions is a new approach to modeling worst-case design problems. Furthermore, modeling process systems--especially those associated with chemical engineering--often results in highly nonconvex functions. The primary contribution of this thesis is a mathematical tool for solving implicit semi-infinite programs and assessing robust feasibility of process systems using a rigorous model-based approach. This tool has the ability to determine, with mathematical certainty, whether or not a physical process system based on the proposed design will fail in the worst case by taking into account uncertainty in the model parameters and uncertainty in the environment. / by Matthew David Stuber. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1992. / Includes bibliographical references (p. 376-384). / by David Charles Gray. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1985. / Bibliography: leaves 529-544. / by Andrew Lawrence Zydney. / Ph.D.